The purpose of this study is three-fold: Firstly, to isolate, purify and chemically characterize the surface antigens of pathogenic Staphylococcus aureus isolated from specimens obtained from human cases of septicemia, osteomyelitis and from deep-seated wounds. Immunochemical, chemical and enzymatic techniques will be employed to analyze the structural features of these antigens. Secondly, to study the immune response to these staphylococcal surface antigens in rabbits and mice. Special emphasis will be made to identify the class of antibodies present in the immune sera and to determine the opsonic properties of these antibodies. In these studies, the in vitro phagocytosis method employing both rabbit and mouse polymorphonuclear leukocytes will be utilized to assay the opsonic capacity of the immune sera obtained from rabbits immunized with pathogenic Staphylococcus aureus. Further, attempts will be made to determine whether or not cellular immunity to these surface antigens exists in rabbits immunized with Staphylococci. In these studies, phagocytes will be obtained from rabbits immunized with Staphylococci, and these leukocytes will then be employed in the in vitro phagocytosis test. The existence of specifically sensitized leukocytes will also be determined by the macrophage inhibition test. Thirdly, to determine the feasibility of employing these surface antigens as a means of classifying S. aureus into distinct groups by a combination of precipitin and immunofluorescent procedures. In these studies, mono-specific fluorescein-labelled antibodies will be employed as a means of grouping the S. aureus isolates from hospitals. Attempts will be made to demonstrate the presence of surface structures on pathogenic Staphylococci by electron microscopy employing specific ferritin-labelled antibody in a manner similar to that described for the detection of M-protein of group A Streptococci and pili of Neisseria gonorrhoeae by Swanson, et al.